Declining olfactory function during aging has a profoundly negative impact on health and life quality. Age-related loss of smell has been proposed to result from compromised olfactory neuron function. The long-term objective of this SBIR research program is to use small-molecule activators of olfactory signal transduction for the commercial application of reversing age-related loss of smell. Significant progress has been made towards this goal by cloning and functionally expressing the cyclic-nucleotide-gated (CNG) channel that mediates olfactory signal transduction in humans. In the first phase of this research program, an optimized cell-based assay for the human olfactory CNG channel will be developed. In subsequent phases, channel activators will be identified by high-throughput screening of volatile chemical libraries; lead activators will be evaluated, optimized, and commercialized as smell enhancers. This research holds great promise for technological innovation because it will produce new assay methods and selective pharmacological agents for CNG channels.